Caveolin 1 has a comparable role as endothelial progenitor cells to repair vascular endothelial dysfunction caused by the combined exposure to arsenic and lipid.

To date, no study has focused on the combined effects of arsenic and lipid exposure on vascular disorders. Substantial evidence indicates that vascular endothelial dysfunction is a primary driver of vascular diseases. Endothelial progenitor cells (EPCs) exert pivotal roles in repairing dysfunctional vascular endothelial cells. Therefore, elucidating the role of EPCs in endothelial dysfunction induced by combined exposure to arsenic and lipid is of great significance. Our results revealed that 25 mg/L sodium arsenite combined with high-fat diet had the most detrimental effect on vascular endothelial function. Exposure to 30 µmol/L NaAsO2+10 µg/mL oxidized low-density lipoprotein, it significantly reduces the cell viability, intracellular NO content, and NOS activity in both mouse aortic endothelial cells and EPCs. Both in vivo and in vitro, a certain number of EPCs could both repair the damaged endothelial function caused by the combined exposure to arsenic and high-fat diet, or oxidized low-density lipoprotein. Proteomic analysis identified Caveolin-1 (Cav-1) as a candidate molecule whose expression was remarkably altered in EPCs under combined exposure, and under 5 µg/mL Cav-1 recombinant protein intervention, the repair ability of EPCs on the dysfunctional mouse aortic endothelial cells was significantly improved. Moreover, 5 µg/mL Cav-1 recombinant protein has comparable repairing effects on endothelial function as intravenous injection of EPCs. Collectively, our systematic studies provide novel promising measures on the prevention and treatment of vascular diseases induced by chronic arsenic exposure and high lipid.